Measurement of enantiomeric excess (ee) of chiral organic compounds is an important analytical problem. For example, enantiomerically pure (or highly enriched) organic compounds are important for many applications, including medicinal chemistry and organic materials chemistry. See Stinson, S.C. “Chiral Drugs,” Chemical and Engineering News 78: 55-78 (200) and Topics in Stereochemistry, Materials-Chirality, Green et al, Eds.; Wiley, 2003; Vol. 24. In these broad classes of applications the quantitative determination of ee is important. Also, sensitive detection of net chirality in materials of low ee may be important in, e.g. detection of enantioenrichment in samples of extraterrestrial organic compounds.
One particularly important current application of the measurement of ee involves combinatorial asymmetric catalyst development. In this application, a library of chiral catalysts is typically applied to an achiral or racemic substrate, producing a library of enantiomerically enriched products. In order to screen the catalyst library for promising leads, the ee of each member of the product library must be determined. Typically, this is accomplished using chromatography on a chiral stationary phase. See Mikes et al, Journal of Chromatography 122 205-221 (1976); Lochmuller et al, Journal of Chromatography 150: 511-514(1978); Pirkle et al, J. Am. Chem. Soc. 103: 3964-3966(1981); Mikes et al, Journal of the Chemical Society-Chemical Communications, 99-100 (1976). However, the chromatographic method is relatively slow, and intrinsically serial in nature, making the determination of ee for a large number samples problematical. While a considerable effort is currently underway in the research community aimed at development of methods for high-throughput measurement of ee, the field of combinatorial asymmetric catalyst development is being seriously hindered due to lack of a method for measurement of ee in tens of thousands of samples in a timely manner. See Reetz et al Chirality 2000, 12, 479-482; Reetz et al, Angew. Chem.-Int. Edit. 2001, 40, 284-310; Shen. et al, Isr. J. Chem. 2001, 41, 313-316; Wahler et al, Current Opinion in Biotechnology 2001, 12, 535-544; Millot et al, Organic Process Research & Development 2002, 6, 463-470; Reetz et al. Advanced Synthesis & Catalysis 2002, 344, 1008-1016; Reetz et al. Chemical Communications 2002, 1428-1429; Schrader et al, Canadian Journal of Chemistry-Revue Canadienne De Chimie 2002, 80, 626-632; Tielmann et al, Chem.-Eur. J. 2003, 9, 3882-3887; Stambuli et al, Current Opinion in Chemical Biology 2003, 7, 420-426; Agarkov et al, Organic Letters 2003, 5, 2091-2094; Traverse & Snapper, Drug Discov. Today 2002, 7, 1002-1012; Miller, Accounts Chem. Res. 2004, 37, 601-610; and Zhu & Anslyn, J. Am. Chem. Soc. 2004, 126, 3676-3677.